VX-745

VX-745 : ATP competitive inhibitor of MAPK14

Structure

SERP Rating

In Cells

(3 ratings)

In Model Organisms

(3 ratings)

note: The Chemical Probes Portal only endorses compounds as chemical probes for use as specific and selective modulators of the proposed target if they receive three or more (3-4) stars.

Information

MAPK14

ATP competitive

50-100 nM

More...

Probe Availability:

In Vitro Validations

Uniprot ID: Q16539

Target Class: Protein kinase

Target SubClass: CMGC

Potency: KD

Potency Value: 2.8 nM

Potency Assay: KD was determined in a kinase binding assay. The IC50 (0.009 uM) was determined using a spectrophotometric coupled-enzyme assay.

PDB ID for probe-target interaction (3D structure): 3FC1

Target aliases:

Mitogen-activated protein kinase 14, SAPK2A, MXI2, ...

In Cell Validations

In Vivo Data

Off-Target Selectivity Assesments

Potency end-point : KD MAPK11 74 nM

Potency assay (off target): VX-745 was 20-fold selective for MAPK14 (p38alpha) > MAPK11 (p38beta) in IC50 assays. VX-745 was tested for kinase binding activity in a panel of 317 kinases showing <10 uM activity against 11 kinases (ABL1, BLK,CSF1R, DDR1, FGR, FYN, LCK, LYN, PDGFRB, SRC, YES).

I have extra information to add

SERP ratings and comments

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

This is a selective probe with some off-target activity against p38β; it is able to cross the blood-brain barrier.

(last updated: 23 Jun 2016 )

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

This probe has a pretty good selectivity towards p38alpha with effects on peripheral blood mononuclear cells (PBMCs) and on a rheumatoid arthritis mouse model.

(last updated: 1 Jul 2016 )

SERP Ratings

In Cell Rating

In Model Organisms

SERP Comments:

Effective inhibition of p38α should be achievable at concentrations between 50-100 nM. The reported Ki for p38β is 220 nM as determined in α spectrophotometric coupled-enzyme assay using recombinant protein. The Kd for other kinases such as DDR1 is reported to be above 1000 nM. This compound is a fairly selective p38 MAPKα inhibitor with a 20-fold window to p38 MAPKβ based on assessment in an activity assay. It is also useful as an in vivo probe.

(last updated: 3 Jul 2017 )

SERP Comments:

This compound is a fairly selective p38 MAPKα inhibitor with a 20-fold window to p38 MAPKβ based on assessement in an activity assay. It is also useful as an in vivo probe.

(last updated: 5 Jul 2017 )